Compounds which contain within their molecular structure a 4-O-methylated phenylethylamine group (e.g. 4-O-methyl dopamine, bulbocapnine, etc.) produce features in animals which mimick the catatonic state sometimes seen in schizophrenia and the bradykinetic-rigid syndrome seen in Parkinson's disease and other basal ganglia disorders. We propose to study in animals the pharmacology and metabolic fate of the amino acids 4-O-methyl dihydroxyphenylalanine (4-O-methyl DOPA) and 4-O-methyl dihydroxyphenylserine (4-O-methyl DOPS), precursors of 4-O-methyl dopamine and 4-O-methyl norepinephrine, respectively. We found that 4-O-methyl DOPA (and probably 4-O-methyl DOPS) readily crosses the blood brain barrier and is decarboxylated to its corresponding amine in the brain. We plan to look for these para O-methylated amines and their metabolites (iso-homovanillic acid, iso-vanillylmandelic acid and iso-methoxy-hydroxyphenylethyleneglycol) in both treated and non-treated animals. We plan also to look for these 4-O-methyl metabolites in human cerebrospinal fluid, and in brain, obtained at post-mortem, of patients with mental and neurologic disorders (e.g. schizophrenia, manic-depressive reaction, Parkinson's disease, on and off L-DOPA). Highly sensitive and specific methods to separate and quantitate these compounds are available in our laboratories. These methods include column chromatography, organic solvent extraction, gas chromatography, with electron capture device, and mass spectrometry when needed. These studies will contribute to the furtherance of our knowledge related to the methylation of biogenic amines in brain and may provide a clue to the pathophysiology of some mental and neurologic disorders.